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Profiling genetic variation along the androgen biosynthesis and metabolism pathways implicates several single nucleotide polymorphisms and their combinations as prostate cancer risk factors.

Mononen, Nina; Seppälä, Eija H; Duggal, Priya; Autio, Ville; Ikonen, Tarja; Ellonen, Pekka; Saharinen, Juha; Saarela, Janna; Vihinen, Mauno LU and Tammela, Teuvo L J, et al. (2006) In Cancer Research 66(2). p.743-747
Abstract
Several candidate genes along androgen pathway have been suggested to affect prostate cancer risk but no single gene seems to be overwhelmingly important for a large fraction of the patients. In this study, we first screened for variants in candidate genes and then chose to explore the association between 18 variants and prostate cancer risk by genotyping DNA samples from unselected (n = 847) and familial (n = 121) prostate cancer patients and population controls (n = 923). We identified a novel single nucleotide polymorphism (SNP) in the CYP19A1 gene, T201M, with a mild significant association with prostate cancer [odds ratio (OR), 2.04; 95% confidence interval (95% CI), 1.03-4.03; P = 0.04]. Stratified analysis revealed that this risk... (More)
Several candidate genes along androgen pathway have been suggested to affect prostate cancer risk but no single gene seems to be overwhelmingly important for a large fraction of the patients. In this study, we first screened for variants in candidate genes and then chose to explore the association between 18 variants and prostate cancer risk by genotyping DNA samples from unselected (n = 847) and familial (n = 121) prostate cancer patients and population controls (n = 923). We identified a novel single nucleotide polymorphism (SNP) in the CYP19A1 gene, T201M, with a mild significant association with prostate cancer [odds ratio (OR), 2.04; 95% confidence interval (95% CI), 1.03-4.03; P = 0.04]. Stratified analysis revealed that this risk was most apparent in patients with organ-confined (T(1)-T(2)) and low-grade (WHO grade 1) tumors (OR, 5.42; 95% CI, 2.33-12.6; P < 0.0001). In contrast, CYP17A1 -34T>C alteration was associated with moderate to poorly differentiated (WHO grade 2-3) organ-confined disease (OR, 1.42; 95% CI, 1.09-1.83; P = 0.007). We also tested a multigenic model of prostate cancer risk by calculating the joint effect of CYP19A1 T201M with five other common SNPs. Individuals carrying both the CYP19A1 and KLK3 -252A>G variant alleles had a significantly increased risk for prostate cancer (OR, 2.87; 95% CI, 1.10-7.49; P = 0.03). In conclusion, our results suggest that several SNPs along the androgen pathway, especially in CYP19A1 and CYP17A1, may influence prostate cancer development and progression. These genes may have different contributions to distinct clinical subsets as well as combinatorial effects in others illustrating that profiling and joint analysis of several genes along each pathway may be needed to understand genetic contributions to prostate cancer etiology. (Less)
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published
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keywords
Androgens: biosynthesis, Aromatase: genetics, Prostatic Neoplasms: genetics, Prostatic Neoplasms: physiopathology, Steroid 17-alpha-Hydroxylase: genetics
in
Cancer Research
volume
66
issue
2
pages
743 - 747
publisher
American Association for Cancer Research Inc.
external identifiers
  • pmid:16424004
  • scopus:31544437147
ISSN
1538-7445
DOI
10.1158/0008-5472.CAN-05-1723
language
English
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no
id
74e6c16f-9d8e-47d0-9307-e8423fe598e6 (old id 3635371)
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http://www.ncbi.nlm.nih.gov/pubmed/16424004?dopt=Abstract
date added to LUP
2013-06-12 16:18:15
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2017-01-01 07:45:36
@article{74e6c16f-9d8e-47d0-9307-e8423fe598e6,
  abstract     = {Several candidate genes along androgen pathway have been suggested to affect prostate cancer risk but no single gene seems to be overwhelmingly important for a large fraction of the patients. In this study, we first screened for variants in candidate genes and then chose to explore the association between 18 variants and prostate cancer risk by genotyping DNA samples from unselected (n = 847) and familial (n = 121) prostate cancer patients and population controls (n = 923). We identified a novel single nucleotide polymorphism (SNP) in the CYP19A1 gene, T201M, with a mild significant association with prostate cancer [odds ratio (OR), 2.04; 95% confidence interval (95% CI), 1.03-4.03; P = 0.04]. Stratified analysis revealed that this risk was most apparent in patients with organ-confined (T(1)-T(2)) and low-grade (WHO grade 1) tumors (OR, 5.42; 95% CI, 2.33-12.6; P &lt; 0.0001). In contrast, CYP17A1 -34T&gt;C alteration was associated with moderate to poorly differentiated (WHO grade 2-3) organ-confined disease (OR, 1.42; 95% CI, 1.09-1.83; P = 0.007). We also tested a multigenic model of prostate cancer risk by calculating the joint effect of CYP19A1 T201M with five other common SNPs. Individuals carrying both the CYP19A1 and KLK3 -252A&gt;G variant alleles had a significantly increased risk for prostate cancer (OR, 2.87; 95% CI, 1.10-7.49; P = 0.03). In conclusion, our results suggest that several SNPs along the androgen pathway, especially in CYP19A1 and CYP17A1, may influence prostate cancer development and progression. These genes may have different contributions to distinct clinical subsets as well as combinatorial effects in others illustrating that profiling and joint analysis of several genes along each pathway may be needed to understand genetic contributions to prostate cancer etiology.},
  author       = {Mononen, Nina and Seppälä, Eija H and Duggal, Priya and Autio, Ville and Ikonen, Tarja and Ellonen, Pekka and Saharinen, Juha and Saarela, Janna and Vihinen, Mauno and Tammela, Teuvo L J and Kallioniemi, Olli and Bailey-Wilson, Joan E and Schleutker, Johanna},
  issn         = {1538-7445},
  keyword      = {Androgens: biosynthesis,Aromatase: genetics,Prostatic Neoplasms: genetics,Prostatic Neoplasms: physiopathology,Steroid 17-alpha-Hydroxylase: genetics},
  language     = {eng},
  number       = {2},
  pages        = {743--747},
  publisher    = {American Association for Cancer Research Inc.},
  series       = {Cancer Research},
  title        = {Profiling genetic variation along the androgen biosynthesis and metabolism pathways implicates several single nucleotide polymorphisms and their combinations as prostate cancer risk factors.},
  url          = {http://dx.doi.org/10.1158/0008-5472.CAN-05-1723},
  volume       = {66},
  year         = {2006},
}